Laboratory of RNA Biology

The focus of the laboratory’s work are the biological functions of RNA; we will use the spliceosome as a model, concentrating on the study of molecular mechanisms that govern pre-mRNA splicing.  Our goal is to understand the complex set of substrate-spliceosome interactions during assembly and catalysis, which affect the positioning of reactive groups at the active site.

We anticipate that our mechanistic studies in yeast will help us to understand the molecular interactions that influence splicing fidelity and alternative splicing in metazoan systems.  We have proposed a two-state model of spliceosome function, according to which substrate selectivity can be modulated by the competition of spliceosomal conformations between the 1st and 2nd step of splicing (Query and Konarska, 2004); studies of some implications of this model form the basis of the lab’s activity.

We are interested in the catalytic center’s general architecture.  We test new models of snRNA:snRNA interactions at the catalytic center, and analyze several spliceosomal factors involved in the substrate positioning for catalysis.  These projects form a part of a broader initiative to develop an orthogonal spliceosome system, in which selected spliceosome mutants function only in the context of a specialized, orthogonal substrate.

To better understand how pre-mRNA is positioned for catalysis, we investiagte exon sequences that compensate for the defects of the 5’SS.  Isolated yeast exon motifs are similar to metazoan exon enhancers; this striking sequence similarity is suggestive of common underlying mechanisms of action. We hypothesize that yeast exon motifs represent substrate binding sites recognized by the spliceosome; we study the molecular mechanisms underlying the function of these motifs.

Prof. Magda Konarska
email: m.konarska@dev.dev.cent.uw.edu.pl/en
phone: +48 22 55 43705
room: 04.165
Education and degrees:
1979 M.Sc. in Biology,  University of Warsaw
1983 Ph.D. in Biochemistry, Institute of Biochemistry and Biophysics,
Polish Academy of Science, Warsaw
2000 Dr hab., Institute of Biochemistry and Biophysics, Warsaw, Poland
Positions:
since 10.2018 Deputy Director “Regenerative Mechanisms for Health”, International Research Agenda Unit (“ReMedy”)
since 2015 Date Professor and Head of Laboratory of RNA Biology, CeNT UW, Warsaw
and Professor Emeritus, The Rockefeller University, New York
2009-2015 Evelyn Gruss-Lipper Professor and Head of Laboratory, The Rockefeller University
2000-2015 Professor and Head of Laboratory, The Rockefeller University
1994-2000 Associate Professor and Head of Laboratory, The Rockefeller University
1989-1994 Assistant Professor and Head of Laboratory, The Rockefeller University
1987-1989 Research Associate in the laboratory of Prof. Phillip A. Sharp, Center for Cancer Research, MIT, Cambridge, MA
1984-1986 Postdoctoral Fellow in the laboratory of Prof. Phillip A. Sharp, Center for Cancer Research, MIT, Cambridge, MA
1979-1983 Ph.D. Student in the laboratory of Prof. Witold Filipowicz, Polish Academy of Sciences, Institute of Biochemistry and Biophysics, Warsaw
1981,82 and 83
(total of nine months)		 Research Fellow in the laboratory of Prof. Hans J. Gross, University of Würzburg, Institute of Biochemistry, Würzburg, West Germany
1979 Research Fellow in the laboratory of Prof. Hans J. Gross, Max-Planck Institute for Biochemistry, Martinsried, West Germany
Memberships and Awards:
2017 Member of the Academia Europaea
2017 Member of the European Molecular Biology Organization
2016 Corresponding Member of the Polish Academy of Science
1992-1997 The Monique Weill-Caulier Career Scientist Award
1987-1994 The Lucille P. Markey Scholar Award
1983-1986 The Jane Coffin Childs Memorial Fund Postdoctoral Fellowship
1985 The Jakub Karol Parnas Award of the Polish Biochemical Society
1983 The Polish Academy of Sciences – Scientific Secretary Award
1982 The Polish Academy of Sciences – Biological Sciences Section Award

 

Selected publications:

  • Konarska, M.M., Filipowicz, W., Domdey, H. and Gross, H.J.  Formation of a 2′-phosphomonoester, 3′,5′-phosphodiester linkage by a novel RNA ligase in wheat germ. Nature 293, 112-116 (1981).
  • Konarska, M.M., Padgett, R.A. and Sharp, P.A.  Recognition of cap structure in splicing in vitro of mRNA precursors. Cell 38, 731-736 (1984).
  • Konarska, M.M., Grabowski, P.J., Padgett, R.A. and Sharp, P.A.  Characterization of the branch site in lariat RNAs produced by splicing of mRNA precursors. Nature 313, 552-557 (1985).
  • Konarska, M.M., Padgett, R.A. and Sharp, P.A.  Trans-splicing of mRNA precursors in vitro.  Cell 42, 165-171 (1985).
  • Konarska, M.M. and Sharp, P.A. Interactions between small nuclear ribonucleoprotein particles in formation of spliceosomes. Cell 49, 763-774 (1987).
  • Konforti, B.B., Koziołkiewicz, M.J. and Konarska, M.M. Disruption of base pairing between the 5′ splice site and the 5′ end of U1 snRNA is required for spliceosome assembly.  Cell 75, 863-873 (1993).
  • Siatecka, M., Reyes, J.L. and Konarska, M.M., Functional interactions of Prp8 with both splice sites at the spliceosomal catalytic center.  Genes & Dev. 13,1983-1993 (1999).
  • Query, C.C. and Konarska, M.M. Suppression of multiple substrate mutations by spliceosomal prp8 alleles suggests functional correlations with ribosomal ambiguity mutants. Molecular Cell 14, 343-354 (2004).
  • Liu, L., Query, C.C. and Konarska, M.M. Opposing classes of prp8 alleles modulate the transition between the catalytic steps of pre-mRNA splicing.  Nature Struct. Mol. Biol. 14,  519-26 (2007).
  • Smith, D.J., Konarska, M.M. and Query, C.C.  Insights into branch nucleophile positioning and activation from an orthogonal pre-mRNA splicing system in yeast.  Molecular Cell  34, 333-343 (2009).
  • Smith, D.J., Query, C.C., and Konarska, M.M. trans-Splicing to Spliceosomal U2 snRNA Suggests Disruption of Branch Site-U2 Pairing during Pre-mRNA Splicing. Mol Cell 2007 Jun 22;26(6):883-90.
  • Query, C.C. and Konarska, M.M. CEF1/CDC5 alleles modulate transitions between catalytic conformations of the spliceosome. RNA 18, 1001-1013 (2012).

Interactions of U6 snRNA within the catalytic center of the spliceosome – modulation of pre-mRNA splicing by U6-like exon sequences

Project Leader: Prof. Magda Konarska Project period: 2013 - 2018
Project funding: MAESTRO, NCN
There are currently no open positions
Anyone interested in joining our lab is encouraged to contact Magda Konarska at m.konarska@dev.dev.cent.uw.edu.pl/en .